Triethylamine → HCID 71278246, compound

HRID 1427401Notes

Reaction equation

HRID 1427401 reaction equation
[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1[S:9][CH2:10][C@@H:11]2[CH2:17][C@H:16]([CH2:18]O)[O:15][CH2:14][C@:12]2([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[N:13]=1)([CH3:4])([CH3:3])[CH3:2].[F:29]C(F)(S(F)(=O)=O)C(F)(F)C(F)(F)C(F)(F)F.F.F.F.C(N(CC)CC)C.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C(#N)C.O1CCCC1>[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1[S:9][CH2:10][C@@H:11]2[CH2:17][C@H:16]([CH2:18][F:29])[O:15][CH2:14][C@:12]2([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[N:13]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 67814Perfluoro-1-butanesulfonyl fluorideHCID 175505N,N-Diethylethanamine trihydrofluorideHCID 516892Sodium BicarbonateHCID 71278245HCID 71278245, compound

Product 1

HCID 71278246HCID 71278246, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl[(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(hydroxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]carbamate (C24) (82 mg, 0.20 mmol) was dissolved in a mixture of acetonitrile (0.8 mL) and tetrahydrofuran (0.2 mL). 1,1,2,2,3,3,4,4,4-Nonafluorobutane-1-sulfonyl fluoride (71.1 μL, 0.396 mmol) was added, followed by triethylamine trihydrofluoride (64.4 μL, 0.395 mmol), and then triethylamine (0.166 mL, 1.19 mmol), and the reaction mixture was allowed to stir at room temperature for 18 hours. Saturated aqueous sodium bicarbonate solution was added, and the mixture was extracted three times with dichloromethane. The combined organic extracts were washed with water, washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification via preparative thin layer chromatography on silica gel (Eluent: 5% methanol in dichloromethane) afforded the product as a pale yellow foam. Yield: 22 mg, 0.053 mmol, 27%. LCMS m/z 415.4 (M−1). 1H NMR (400 MHz, CDCl3), characteristic peaks: δ 1.53 (s, 9H), 1.87-1.99 (m, 1H), 2.57 (dd, J=12.9, 2.8 Hz, 1H), 2.93 (dd, J=12.9, 3.8 Hz, 1H), 3.01-3.10 (br m, 1H), 3.79 (br d, J=12 Hz, 1H), 3.91-4.03 (m, 1H), 4.15 (dd, J=11.9, 1.9 Hz, 1H), 4.42 (ddd, half of ABXY pattern, J=46.7, 9.9, 3.6 Hz, 1H), 4.50 (ddd, half of ABXY pattern, J=47.7, 9.9, 6.4 Hz, 1H), 6.85 (ddd, J=12.4, 8.4, 2.4 Hz, 1H), 6.89-6.96 (m, 1H), 7.28-7.36 (m, 1H).

Workup

  1. extractionthe mixture was extracted three times with dichloromethane
  2. washThe combined organic extracts were washed with water
  3. washwashed with saturated aqueous sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification via preparative thin layer chromatography on silica gel (Eluent: 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-15ddd741476647c2aced9239d0948085
Source dataset
uspto-grants-2015_01
Patent number
US08933221B2

Reaction notes

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